深入脑血管脂质组学分析,发现莫亚莫亚和颅内动脉粥样硬化疾病的新型生物标记物和机制。

IF 12.5 2区 医学 Q1 SURGERY International journal of surgery Pub Date : 2024-10-01 DOI:10.1097/JS9.0000000000002092
Kangmin He, Xinmei Wang, Yu Gu, Xiao Tong, Xuanfeng Qin, Yujun Liao, Li-Hao Huang, Jiaxi Wang, Bin Xu
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引用次数: 0

摘要

背景:尽管开展了大量研究工作,但人们对导致莫亚莫亚病(MMD)的确切病因和潜在途径仍然知之甚少。此外,MMD 和颅内动脉粥样硬化性疾病(ICAD)的血管病理相互重叠,这给临床鉴别带来了挑战,即使是采用金标准脑血管造影术也是如此。对颅内多发性硬化症(MMD)脑血管脂质体改变的深入研究可为了解多发性硬化症相关机制(包括多发性硬化症和颅内动脉粥样硬化症)的发病机制提供有价值的见解,并揭示新的生物标志物和潜在的治疗靶点。然而,迄今为止还缺乏全面的脂质组学分析:为了发现新的生物标志物并揭示MMD的病理生理机制,我们进行了脂质组学分析,以确定来自确诊为MMD(99人)和ICAD(12人)患者的匹配人体颅外和颅内动脉组织中各种脂质的特征:结果:我们的分析鉴定出了569种脂质,并根据接收者操作特征曲线分析,确定了一组能够有效区分MMD和ICAD的脂质体生物标志物(曲线下面积=0.98)。值得注意的是,与 ICAD 患者相比,我们观察到 MMD 患者颅内动脉组织中的二酰甘油呈明显的正相关,而甘油三酯呈负相关,这表明二酰甘油诱导的信号传导失调在 MMD 发病机制中可能起了作用。此外,我们对MMD和ICAD患者颅内动脉血管脂质种类的临界差异与临床参数的相关性进行了调查,结果显示与血浆铁水平呈负相关,这意味着在MMD发病过程中,血浆铁代谢与动脉脂质平衡之间存在潜在联系:这些研究结果为临床诊断提供了广阔的前景,有助于更好地区分这两种疾病。结论:这些发现为临床诊断提供了广阔的前景,有助于加强对这两种疾病的鉴别。此外,它们还揭示了MMD发病的基本机制,并提出了针对动脉血管脂质或血浆铁水平的潜在治疗途径。
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In-depth cerebrovascular lipidomics profiling for discovering novel biomarkers and mechanisms in moyamoya and intracranial atherosclerotic disease.

Background: Despite considerable research efforts, the precise etiology and underlying pathways contributing to Moyamoya Disease (MMD) remain poorly understood. Moreover, the overlapping vascular pathologies shared between MMD and Intracranial Atherosclerotic Disease (ICAD) pose challenges in clinical differentiation, even with gold-standard cerebral angiography. An in-depth exploration of lipidomic alterations in cerebral intracranial MMD vessels could offer valuable insights into the pathogenesis of MMD-related mechanisms, encompassing MMD and ICAD, and unveil novel biomarkers and potential therapeutic targets. However, to date, comprehensive lipidomic profiling has been lacking.

Materials and methods: To discover novel biomarkers and unravel the pathophysiological mechanisms underlying MMD, we conducted a lipidomics analysis to characterize various lipid species in matched human extracranial and intracranial artery tissues from patients diagnosed with MMD (n=99) and ICAD (n=12).

Results: Our analysis identified 569 lipid species and delineated a robust panel of lipidomic biomarkers capable of effectively distinguishing MMD from ICAD (area under curve=0.98), as determined by receiver operating characteristic curve analysis. Notably, we observed a significantly more pronounced positive correlation of diacylglycerols and a negative association of triglycerides in intracranial artery tissues of MMD patients compared to those with ICAD, suggesting a potential role of dysregulated diacylglycerol-induced signaling in MMD pathogenesis. Furthermore, our investigation into the correlations of critical differential intracranial artery vessel lipid species between MMD and ICAD and clinical parameters revealed negative associations with plasma iron levels, implying a potential link between plasma iron metabolism and artery lipid homeostasis during MMD pathogenesis.

Conclusion: These findings offer promising prospects for advancing clinical diagnosis for enhanced differentiation between the two disease conditions. Additionally, they shed light on the fundamental mechanisms implicated in MMD pathogenesis and suggest potential therapeutic avenues through targeting artery vessel lipids or plasma iron levels.

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来源期刊
CiteScore
17.70
自引率
3.30%
发文量
0
审稿时长
6-12 weeks
期刊介绍: The International Journal of Surgery (IJS) has a broad scope, encompassing all surgical specialties. Its primary objective is to facilitate the exchange of crucial ideas and lines of thought between and across these specialties.By doing so, the journal aims to counter the growing trend of increasing sub-specialization, which can result in "tunnel-vision" and the isolation of significant surgical advancements within specific specialties.
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